An Effective Synthesis of Previously Unknown 7-Aryl Substituted Paullones

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Mar 11

PMID 36903571

Authors

Dmitrii A Aksenov

Alesia S Akulova

Elena A Aleksandrova

Nicolai A Aksenov

Alexander V Leontiev

Alexander V Aksenov

Affiliations

Soon will be listed here.

Abstract

A straightforward three-step procedure affording a wide range of novel 7-aryl substituted paullone derivatives was developed. This scaffold is structurally similar to 2-(1-indol-3-yl)acetamides-promising antitumor agents-hence, could be useful for the development of a new class of anticancer drugs.

Citing Articles

Design and application of intramolecular arylogous nitroaldol condensation to access 2-aryl-benzofuran and -indole derivatives and formal synthesis of saprisartan.

Reddy M, Satyam K, Suresh S RSC Adv. 2024; 14(50):37234-37239.

PMID: 39569112 PMC: 11577158. DOI: 10.1039/d4ra07741e.

References

Kunick C, Lauenroth K, Wieking K, Xie X, Schultz C, Gussio R . Evaluation and comparison of 3D-QSAR CoMSIA models for CDK1, CDK5, and GSK-3 inhibition by paullones. J Med Chem. 2003; 47(1):22-36. DOI: 10.1021/jm0308904. View

Yuskaitis C, Jope R . Glycogen synthase kinase-3 regulates microglial migration, inflammation, and inflammation-induced neurotoxicity. Cell Signal. 2008; 21(2):264-73. PMC: 2630396. DOI: 10.1016/j.cellsig.2008.10.014. View

Fischer P, Lane D . Inhibitors of cyclin-dependent kinases as anti-cancer therapeutics. Curr Med Chem. 2000; 7(12):1213-45. DOI: 10.2174/0929867003374048. View

Aksenov A, Aksenov D, Arutiunov N, Aksenov N, Aleksandrova E, Zhao Z . Synthesis of Spiro[indole-3,5'-isoxazoles] with Anticancer Activity via a Formal [4 + 1]-Spirocyclization of Nitroalkenes to Indoles. J Org Chem. 2019; 84(11):7123-7137. DOI: 10.1021/acs.joc.9b00808. View

Falke H, Chaikuad A, Becker A, Loaec N, Lozach O, Abu Jhaisha S . 10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acids are selective inhibitors of DYRK1A. J Med Chem. 2015; 58(7):3131-43. PMC: 4506206. DOI: 10.1021/jm501994d. View

Orban O, Korn R, Benitez D, Medeiros A, Preu L, Loaec N . 5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms. Bioorg Med Chem. 2016; 24(16):3790-800. DOI: 10.1016/j.bmc.2016.06.023. View

Power D, Lozach O, Meijer L, Grayson D, Connon S . Concise synthesis and CDK/GSK inhibitory activity of the missing 9-azapaullones. Bioorg Med Chem Lett. 2010; 20(16):4940-4. DOI: 10.1016/j.bmcl.2010.06.024. View

Gong L, Hirschfeld D, Tan Y, Hogg J, Peltz G, Avnur Z . Discovery of potent and bioavailable GSK-3beta inhibitors. Bioorg Med Chem Lett. 2010; 20(5):1693-6. DOI: 10.1016/j.bmcl.2010.01.038. View

Lee S, Lee S, Choi E, Ham O, Lee C, Lee J . Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury. Sci Rep. 2016; 6:23472. PMC: 4806297. DOI: 10.1038/srep23472. View

10.

Leost M, Schultz C, Link A, Wu Y, Biernat J, Mandelkow E . Paullones are potent inhibitors of glycogen synthase kinase-3beta and cyclin-dependent kinase 5/p25. Eur J Biochem. 2000; 267(19):5983-94. DOI: 10.1046/j.1432-1327.2000.01673.x. View

11.

Knockaert M, Wieking K, Schmitt S, Leost M, Grant K, Mottram J . Intracellular Targets of Paullones. Identification following affinity purification on immobilized inhibitor. J Biol Chem. 2002; 277(28):25493-501. DOI: 10.1074/jbc.M202651200. View

12.

Aksenov A, Kirilov N, Arutiunov N, Aksenov D, Kuzminov I, Aksenov N . Reductive Cleavage of 4'-Spiro[indole-3,5'-isoxazoles] En Route to 2-(1-Indol-3-yl)acetamides with Anticancer Activities. J Org Chem. 2022; 87(21):13955-13964. DOI: 10.1021/acs.joc.2c01627. View

13.

Aksenov N, Aksenov A, Prityko L, Aksenov D, Aksenova D, Nobi M . Oxidative Cyclization of 4-(2-Aminophenyl)-4-oxo-2-phenylbutanenitriles into 2-(3-Oxoindolin-2-ylidene)acetonitriles. ACS Omega. 2022; 7(16):14345-14356. PMC: 9089741. DOI: 10.1021/acsomega.2c01238. View

14.

Guendel I, Agbottah E, Kehn-Hall K, Kashanchi F . Inhibition of human immunodeficiency virus type-1 by cdk inhibitors. AIDS Res Ther. 2010; 7(1):7. PMC: 2852372. DOI: 10.1186/1742-6405-7-7. View

15.

Aksenov A, Smirnov A, Aksenov N, Aksenova I, Frolova L, Kornienko A . Metal-free transannulation reaction of indoles with nitrostyrenes: a simple practical synthesis of 3-substituted 2-quinolones. Chem Commun (Camb). 2013; 49(81):9305-7. PMC: 4945960. DOI: 10.1039/c3cc45696j. View

16.

Harish B, Subbireddy M, Suresh S . N-Heterocyclic carbene (NHC)-catalysed atom economical construction of 2,3-disubstituted indoles. Chem Commun (Camb). 2017; 53(23):3338-3341. DOI: 10.1039/c6cc10292a. View

17.

Arun V, Pilania M, Kumar D . Access to 2-Arylindoles via Decarboxylative C-C Coupling in Aqueous Medium and to Heteroaryl Carboxylates under Base-Free Conditions using Diaryliodonium Salts. Chem Asian J. 2016; 11(23):3345-3349. DOI: 10.1002/asia.201601290. View

18.

Aksenov A, Aksenov N, Aksenov D, Khamraev V, Rubin M . Nitrostyrenes as 1,4-CCNO-dipoles: diastereoselective formal [4+1] cycloaddition of indoles. Chem Commun (Camb). 2018; 54(94):13260-13263. DOI: 10.1039/c8cc07451h. View

19.

Sielecki T, Boylan J, Benfield P, Trainor G . Cyclin-dependent kinase inhibitors: useful targets in cell cycle regulation. J Med Chem. 2000; 43(1):1-18. View

20.

Aksenov N, Aksenov D, Skomorokhov A, Prityko L, Aksenov A, Griaznov G . Synthesis of 2-(1-Indol-2-yl)acetamides via Brønsted Acid-Assisted Cyclization Cascade. J Org Chem. 2020; 85(19):12128-12146. DOI: 10.1021/acs.joc.0c01344. View